DESCRIPTION The goal of this proposed research is to determine whether 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD)-induced oxidative stress leads to the development of insulin resistance. The mouse pre-adipocyte cell line (3T3-L1) will be used as an in vitro model system to study TCDD-induction of insulin resistance. The goal of this research will be pursued through studies in two specific aims. The first aim is to determine whether TCDD exposure leads to insulin resistance in 3T3-L1 cells by inducing oxidative stress. The effects of TCDD on activity and mRNA levels of the antioxidant glutathione peroxidase (GSH-PX), catalase, and superoxide dismutase will be evaluated. Additionally, evidence of oxidative damage will be assessed by measuring lipid peroxidation and DNA strand breaks. The second aim is designed to determine whether TCDD-induced insulin resistance in 3T3-L1 cells can be blocked by overexpression of GSH-Px.